|Year : 2020 | Volume
| Issue : 4 | Page : 155-160
Acute Decompensated Heart Failure with Reduced Ejection Fraction: Common Etiological Cause and Predictor of Mortality in the Nepalese Population
Rajesh Nepal MD, DM , Manoj Kumar Choudhary MD , Sushant Katuwal MD , Sunil Babu Khanal MBBS , Roshna Adhikari MBBS , Madhav Bista MD , Sahadev Dhungana MD, DM
Department of Internal Medicine, Cardiology Unit, Nobel Medical College Teaching Hospital, Biratnagar, Nepal
|Date of Submission||23-Jun-2020|
|Date of Decision||04-Aug-2020|
|Date of Acceptance||11-Sep-2020|
|Date of Web Publication||09-Feb-2021|
Dr. Rajesh Nepal
Department of Internal Medicine, Cardiology Unit, Nobel Medical College Teaching Hospital, Biratnagar
Source of Support: None, Conflict of Interest: None
Background: Heart failure with reduced ejection fraction (HFrEF) is one of the most common cardiac diseases causing hospital admission, with a very high short- and long-term mortality rate. The study aims to assess the short-term mortality rate of acute decompensated HFrEF and its correlation with the baseline characteristics in a Nepalese population. Methods: Patients with acute decompensated HFrEF admitted in the unit were prospectively enrolled in this study and were followed up for 3 months. Patients who died and those who did not die were compared using the Chi-square test for categorical variables and Student's t-test was used for the comparison of continuous variables. Results: A total of 100 patients were included in the study. The mean age of the patient was 60 ± 16.18 years, with 55% of the participants being male. Atrial fibrillation was documented in 17% and 16% had bundle branch block. Idiopathic dilated cardiomyopathy was seen in 56% of the participants and was found to be the most common cause of HFrEF, followed by coronary artery disease (18%). Pleural effusion was present in 17% of the patients, out of which bilateral effusion was more common (8%). Twenty-nine percent of the patients died during the 3 months follow-up period. Dyslipidemia, hypertension, ejection fraction, baseline hemoglobin, and creatinine level were significant predictors for mortality (P < 0.05 for all). Conclusion: Dilated cardiomyopathy was the most common cause of acute decompensated HFrEF in the Nepalese population. A very high 3-month mortality rate (29%) was recorded. The presence of cardiovascular risk factors, reduced ejection fraction, baseline hemoglobin, and creatinine levels were significant predictors of mortality in acute decompensated HFrEF patients.
Keywords: Cardiovascular risk factors, heart failure, mortality, reduced ejection fraction
|How to cite this article:|
Nepal R, Choudhary MK, Katuwal S, Khanal SB, Adhikari R, Bista M, Dhungana S. Acute Decompensated Heart Failure with Reduced Ejection Fraction: Common Etiological Cause and Predictor of Mortality in the Nepalese Population. J Clin Prev Cardiol 2020;9:155-60
|How to cite this URL:|
Nepal R, Choudhary MK, Katuwal S, Khanal SB, Adhikari R, Bista M, Dhungana S. Acute Decompensated Heart Failure with Reduced Ejection Fraction: Common Etiological Cause and Predictor of Mortality in the Nepalese Population. J Clin Prev Cardiol [serial online] 2020 [cited 2022 Jan 26];9:155-60. Available from: https://www.jcpconline.org/text.asp?2020/9/4/155/308978
| Introduction|| |
Heart failure (HF) is considered as an emerging epidemic, affecting around 26 million people worldwide. It is a common cardiovascular condition with increasing incidence and prevalence. In India, annually, 491600-1.8 million are diagnosed with HF due to various causes such as coronary artery disease (CAD), hypertension, obesity, diabetes, and rheumatic heart disease (RHD), although it may be still underestimated. After the diagnosis of HF, crude case fatality rates have been reported to be 20% and 45%, at 30 days and at 1 year, respectively. A reduced left ventricular ejection fraction (LVEF) was found to be associated with an increased risk of sudden death., In HF patients, younger age was a powerful predictor of survival. Anemia has also been associated with higher HF severity and mortality in some studies. Similarly, the creatinine levels are considered prognostic factors in hospitalized patients with HF.,, A previous study from Nepal reported in-hospital mortality of 9.4% in HF patients. Although the overall prevalence of RHD is still higher in Nepal and was one of the most common causes of HF previously, the incidence of CAD is on rise in Nepal., More than 60% of patients with HF in the US might be attributable to CAD compared to the other risk factors such as hypertension, obesity, diabetes, and smoking., However, a recently published study from Nepal reported idiopathic dilated cardiomyopathy (DCM) accounting for 50% of all clinically diagnosed causes for HF patients. Despite advances in the treatment, chronic HF with systolic dysfunction remain at high risk for re-hospitalization and higher mortality., This may be attributed to the advanced age of the population, progressive disease, and persistently high event rates.
To the best of our knowledge, there is a paucity of data related to etiological factors and predictors of mortality in acute decompensated HF patients in Nepal. Our study aims to assess 90-day outcomes in patients with HFrEF admitted with New York Heart Association (NYHA) class III/IV and the factors associated with re-admissions and mortality.
| Methods|| |
This was a prospective descriptive study done at Nobel Medical College, Biratnagar for 18 months. A cohort of 100 consecutive eligible patients with a primary diagnosis of HF with reduced ejection fraction (HFrEF) who were discharged from our cardiac care unit were selected. The diagnosis of acute decompensated HFrEF was made by cardiologists based on the HF guidelines. Inclusion criteria were age >16 years, NYHA III/IV, LVEF <45%. Chronic organ failure like chronic kidney disease requiring dialysis, chronic liver disease, advanced chronic obstructive pulmonary disease with cor-pulmonale, nonambulating stroke, HF with preserved ejection fraction (HFpEF) and those not willing to give consent were excluded. LVEF was calculated on echocardiography by the eyeballing method by expert operators. All enrolled patients were evaluated clinically and all of them underwent routine cardiac investigations and echocardiography (first assessment). The study complies with the declaration of Helsinki and was approved by the ethical committee of the Nobel Medical College Teaching Hospital. Signed informed consent was obtained from all participants.
The patients were followed up for 3 months on their follow-up visits in outpatient department, subsequent readmissions and/or through telephonic calls.
Ischemic heart disease heart failure
HF patients admitted with a history of chronic stable angina or acute coronary syndrome or with evidence of significant CAD by coronary angiogram were labeled as ischemic heart disease HF.
Idiopathic/dilated cardiomyopathy-heart failure
Patients with DCM and or no obvious cause of HF were found.
Valvular heart disease
Left ventricular systolic dysfunction in the presence of a significant valvular lesion.
Alcoholic heart failure
HF in the presence of significant alcohol consumption and no other obvious cause.
HF beginning at 1-month prior or 5-month postpartum period.
Any of the following values in fasting sample taken within 24 h of the event were as follows: total cholesterol ≥200 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, triglycerides ≥150 mg/dL, and high-density lipoprotein cholesterol ≤40 mg/dL or patients already on medication for dyslipidemia.
Hypertension included systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg and/or concomitant use of antihypertensive medications.
Optimal medical management was defined as a combination of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and aldosterone receptor blockers in patients with left ventricular systolic dysfunction (LVSD, EF < 45%). This was in addition to diuretics and digoxin, as and when necessary.
The demographic, laboratory, and echocardiographic data were analyzed using analysis of variance (ANOVA), and the Bonferroni correction was applied in the post hoc analyses. Categorical variables were reported as a percentage (%), and continuous variables were reported as the mean ± standard error of the mean. Groups were compared using the Chi-square test (cross-tabulation method) for categorical variables and Student's t-test was used for the comparison of continuous variables. P < 0.05 was considered statistically significant, with a 95% confidence interval. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 17.0 for Windows (SPSS, Inc., Chicago, Illinois, and the USA).
| Results|| |
Demographic and study characteristics
Altogether, 100 patients were included in this study, with equally divided male and female ratio. The mean age of the patient was 60 ± 16.18 years (male 61.18 ± 15.76, female 58.28 ± 16.60). Among the enrolled HF patients, 55% of patients aged > 60 years of age. Both age and sex did not correlate significantly with mortality (P = 0.25 and 0.36 respectively). The age distribution chart is presented in [Figure 1].
Laboratory and chest X-ray findings
Twenty-four percent of the patients with acute decompensated HF had a history of hypertension; among them, 48% of patients who expired had a history of hypertension, whereas dyslipidemia was observed in 66% of patients who expired. Seventeen percent of the patient had pleural effusion in chest X-ray. Eight percent of the patients had bilateral pleural effusion, while 6% had only right and 3% had isolated left-sided pleural effusion [Table 1]. The mean hemoglobin level of the study population was 11.92 ± 2.12 g/dL. Mean hemoglobin in survival group was higher (12.16 g/dL) compared to that in expired group (11.35 g/dL) (P = 0.020). The mean creatinine of the study population was 1.49 ± 0.95 mg/dL. Survival group had mean creatinine lower (1.37 mg/dL) compared to expired group (1.81 mg/dL) (P = 0.038) [Table 2].
Electrocardiogram and echocardiographic findings
Atrial fibrillation (AF) was reported in 17 patients, 16 patients had conduction abnormality out of which fifteen had left bundle branch block (LBBB) and one patient had right bundle branch block. Both AF and conduction defects did not correlate positively with mortality [Table 1].
Mean LVEF was 24.99 ± 6.57%, while mean pulmonary artery systolic pressure was 36.13 ± 8.03 mmHg. The mean left ventricle end-diastolic diameter (LVEDD) was 58.18 ± 8.56 mm, while the mean left atrium (LA) size was 40.02 ± 8.08 mm. Pericardial effusion was present in 11% of the patient. Mild mitral regurgitation (MR) was present in 34%, moderate in 34%, and severe MR in 6%. None of the echocardiographic parameters except ejection fraction correlated positively with mortality [Table 1] and [Table 2].
Hospital stay and mortality
There was no significant difference in the duration of hospital stay in both survivals (4 ± 3 days) versus expired group (5 ± 3 days). Ninety days mortality rate in acute decompensated HF patients was 29% of the total population. The mortality rate was not different between male (17%) and female (12%) HF patients. The mean age in the dead patient's group was 62 years, while in the survival group, it was 59 years [Table 1]. History of hypertension and dyslipidemia were significantly associated with mortality (P ≤ 0.004 for both). Hemoglobin less than 12 g/dL, and creatinine more than 1.2 mg/dL were also significantly associated with higher mortality (P ≤ 0.038 for both). LVEF was the strong predictor of mortality in HF patients (P = 0.039) [Table 3].
Etiologies of heart failure
In majority of the patients, definitive etiology could not be determined and hence were considered idiopathic DCM (56%). DCM was considered to be the most common cause of HF in the Nepalese population. CAD was diagnosed either by coronary angiography or if the clinical symptoms, electrocardiogram (ECG), and Echocardiographic findings are consistent with CAD. In this study, 18% of HF patients were diagnosed with ischemic cardiomyopathy. Twelve patients were diagnosed as alcoholic cardiomyopathy. Eight patients had valvular heart disease, mostly RHD and four patients had peripartum cardiomyopathy (PPCM). Most of these diagnosed patients also had hypertension and among them, only two patients (2%) were considered hypertensive cardiomyopathy with a history of long-term hypertension and absence of other likely causes among 24 hypertensive subjects [Table 4]. None of the etiology significantly correlates with mortality (P = 0.45). Among the 100 patients enrolled in this study, only twelve patients among the HF patients underwent coronary angiography.
Optimal medical therapy
All patients with HF could not receive goal-directed optimal medical therapy because of comorbidities and/or they could not tolerate it. Ninety-four percent of the patients received loop diuretics (furosemide or torsemide) at discharge. Aldosterone antagonist was prescribed in 78% of the patients. Fifty-seven percent of the patient received ACEI/ARB, while only 42% received beta-blockers. Sixty-three percent of the patients were getting digoxin, while only one patient received implantable cardioverter-defibrillator [Table 5].
| Discussion|| |
HF is a serious public health burden with patients having poor quality of life and shorter life expectancy compared to the general population. Due to an increasing life expectancy of the Nepalese population and comparatively progressive improvement in survival after acute myocardial infarction, it could be inevitable that HF will continue to be an important public health challenge in the near future. In our present study, 29% of the patients died in 3 months follow up period. Similar to our findings, a study reported 27% mortality in 90 days in ischemic HF patients. In another study from India, 8.5% in-hospital mortality was recorded in 90 days but did not provide data for overall mortality outside the hospital. In this study, HFpEF (≥45%) accounted for 26% of the total population. The high number of 3-month mortality in our study can be attributed to various reasons. HF patients of our study were very sick, as evidenced by advanced NYHA class at admission (93% at NYHA IV), higher mean LVEDD (59 mm) and higher creatinine, while lower hemoglobin level.
A large northern Europe observational study reported DCM as the cause of HF in 7.9% of patients admitted to the hospital. Whereas, recently in Nepal, Manandhar et al. reported DCM accounted for 50% of total HF cases reported. In agreement with above study from Nepal, even in our present study, the majority of the patients were considered idiopathic DCM (56%). The number of reported DCM cases was quite higher than in general. CAD is one of the main causes of HF worldwide.,,, Whereas in contrast to previous studies, the prevalence of CAD was low (18%) in the present study. Only 12% of the subjects among the total patients enrolled had undergone CAG in the current study. As the LVEF goes down, it is not easy to appreciate regional wall motion abnormalities in echocardiography, and ECG may remain inconclusive in the presence of triple vessel disease. Moreover, history alone is not sufficient for diagnosing CAD. This might have led to some underestimation of CAD in our study, but still, it is less compared to the western studies.,,, RHD accounted for 8% of total cases in the present study. However, Regmi et al. in 2009 reported that RHD was the major cause in HF patients, accounting for 45% of total cases. RHD is still common in the Nepalese population, but with much advancement in health facility since 2009, with better diagnostics and management, early medical attention and detection of subclinical carditis, and long-term anticoagulation therapy, a decreased risk of complication and overall mortality has been seen., Our results reported that alcohol abuse accounts for 12% of all HF patients. Alcohol use disorders have been on the rise in Nepal, with one in four/five men who consume alcohol are likely to have alcohol use disorders., Due to chronic alcohol abuse, there is an increase in blood pressure with weaker immune systems, which could lead to increased susceptibility to infections, which in turn could add to the development of HF. As our hospital is a high volume birth center, we found four patients with PPCM in such a short period. However, none of the etiology significantly correlated with mortality (P = 0.45). Our results are in contrast to Pocock et al., who reported that previous myocardial infarction, an ischaemic etiology of HF, was independent predictor mortality. The result of nonsignificant outcome on basis of the etiology could be due to a small sample size and shorter duration of follow up.
Arrhythmia is a common finding in HF. In fact, completely normal ECG virtually rules out HF. In this study, 17% of the participants had AF and 16% had conduction abnormity, mainly LBBB. Pericardial effusion was present in 11% of the patient. Mild MR was present in 34%, moderate in 34%, and severe MR in 6%. Previous studies have reported ischemic etiology of HF, AF, MR, and bundle branch block as a predictor of worse outcome., In our present study, none of the ECG and echocardiographic parameters except ejection fraction correlated positively with mortality.
In the present study, 55% of HF patients were >60 years of age, with 55 male and 45 female patients. Previous studies have reported advancing age, male sex, and lower LVEF as one of the most common predictors for HF death.,,,, However, in our present study though the number of death in males was numerically higher compared to females, it was not statistically significant. Similarly, advancing age was not significantly associated with mortality. Further studies are required with a larger number of a sample size to clarify the advancing age and male sex association with mortality in the Nepalese population. HF with systolic dysfunction is considered to have a poorer prognosis despite therapeutic advancement., The ECHOES mortality data reported poorer prognosis in HF patients with reduced LVEF compared to those with HF with normal LVEF. In agreement, our study also reported a high mortality rate in patients with reduced LVEF. Hobbs et al. reported a survival rate of 83% in those with EF 41%–50%, and 65% in those with <40%. Furthermore, in a large congestive HF population study, it reported an increase in 14% mortality rate for every 5% decrease in EF below 45%.
Studies have suggested that anemia increases the risk of CVD and mortality in chronic kidney disease or HF patients.,, Renal dysfunction is very common in HF patients. It is associated with high morbidity and mortality. Through multiple mechanisms, cardiac and renal dysfunction may worsen each other. Fluid overload, increased venous pressure, hypo-perfusion, neurohormonal or inflammatory activation, and concomitant treatment might be some of the underlying causes. In the current study, HF patients with mean hemoglobin < 12 g/dL and mean creatinine level more than 1.2 mg/dL at admission was significantly associated with increased mortality (P = 0.02). Our center observance to guideline-directed medical therapy with HF was in comparable to international studies guidelines.
The strength of the present study is it presents the real-world data of the region. It gives the outcome of 3-month follow-up of the HFrEF patients presenting in NYHA IV. One major limitation of the study is the lack of adequate coronary angiography. Many patients in the study labeled as idiopathic DCM may, in fact, be ischemic cardiomyopathy. Small sample size and inadequate therapy (lack of device therapy in eligible patients), and visually estimated LVEF are other limitations of the study.
| Conclusion|| |
DCM was the most common cause of acute decompensated HFrEF in the Nepalese population and had a very high 3-month mortality rate (29%). The presence of cardiovascular risk factors, such as hypertension and dyslipidemia, ejection fraction, hemoglobin, and creatinine level, was significant predictors of mortality in HFrEF patients. This study also highlights the importance of performing coronary angiography in Nepalese HFrEF patients for better etiological understanding.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ponikowski P, Anker SD, AlHabib KF, Cowie MR, Force TL, Hu S, et al
. Heart failure: Preventing disease and death worldwide. ESC Heart Fail 2014;1:4-25.
Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev 2017;3:7-11.
Huffman MD, Prabhakaran D. Heart failure: Epidemiology and prevention in India. Natl Med J India 2010;23:283-8.
MacIntyre K, Capewell S, Stewart S, Chalmers JW, Boyd J, Finlayson A, et al
. Evidence of improving prognosis in heart failure: Trends in case fatality in 66 547 patients hospitalized between 1986 and 1995. Circulation 2000;102:1126-31.
Chugh SS, Reinier K, Teodorescu C, Evanado A, Kehr E, Al Samara M, et al
. Epidemiology of sudden cardiac death: Clinical and research implications. Prog Cardiovasc Dis 2008;51:213-28.
Nepal R, Choudhary MK, Dhungana S, Katwal S, Khanal S, Bista M, et al
. Prevalence and major cardiac causes of cardio-embolic stroke and in-hospital mortality in Eastern Nepal. J Clin Prev Cardiol 2020;9:19-24. [Full text]
Hajouli S, Ludhwani D. Heart failure and ejection fraction. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
Lee G, Choi S, Kim K, Yun JM, Son JS, Jeong SM, et al
. Association of hemoglobin concentration and its change with cardiovascular and all-cause mortality. J Am Heart Assoc 2018;7:e007723. [doi: 10.1161/JAHA.117.007723].
McDonagh T, Damy T, Doehner W, Lam CS, Sindone A, van der Meer P, et al
. Screening, diagnosis and treatment of iron deficiency in chronic heart failure: Putting the 2016 European Society of Cardiology heart failure guidelines into clinical practice. Eur J Heart Fail 2018;20:1664-72.
Regmi SR, Maskey A, Dubey L. Heart failure Study: Profile of heart failure admissions in medical intensive Care unit. Nepal Heart J 2017;6:32-4.
Vaidya A. Tackling cardiovascular health and disease in Nepal: Epidemiology, strategies and implementation. Heart Asia 2011;3:87-91.
He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 2001;161:996-1002.
Pocock SJ, Wang D, Pfeffer MA, Yusuf S, McMurray JJ, Swedberg KB, et al
. Predictors of mortality and morbidity in patients with chronic heart failure. Eur Heart J 2006;27:65-75.
Manandhar R, Bogati A, Prajapati D, Aslam S, Choudhary T, Mahat S, et al
. Adherence to guideline-directed medical therapy among left ventricular systolic dysfunction patients in Shahid Gangalal National Heart Centre, Kathmandu, Nepal. Nepalese Heart J 2020;17:29-32.
O'Connor CM, Whellan DJ, Wojdyla D, Leifer E, Clare RM, Ellis SJ, et al
. Factors related to morbidity and mortality in patients with chronic heart failure with systolic dysfunction: The HF-ACTION predictive risk score model. Circ Heart Fail 2012;5:63-71.
Hobbs FD, Roalfe AK, Davis RC, Davies MK, Hare R, Midlands Research Practices Consortium (MidReC). Prognosis of all-cause heart failure and borderline left ventricular systolic dysfunction: 5 year mortality follow-up of the Echocardiographic Heart of England Screening Study (ECHOES). Eur Heart J 2007;28:1128-34.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al
. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129-200.
Om Murti A, Sayami A, Nepal R, Bhattarai N, Chaudhary N. Primary percutaneous coronary intervention for the treatment of acute ST-segment elevated myocardial infarction: Initial single-center experience from Kathmandu, Nepal. J Clin Prev Cardiol 2018;7:132-6.
Suman OS, Vijayaraghavan G, Muneer AR, Ramesh N, Harikrishnan S, Kalyagin AN. Long-term outcomes of patients admitted with heart failure in a tertiary care center in India. Indian Heart J 2018;70 Suppl 1:S85-9.
Harikrishnan S, Sanjay G, Anees T, Viswanathan S, Vijayaraghavan G, Bahuleyan CG, et al
. Clinical presentation, management, in-hospital and 90-day outcomes of heart failure patients in Trivandrum, Kerala, India: The Trivandrum Heart Failure Registry. Eur J Heart Fail 2015;17:794-800.
Pecini R, Møller DV, Torp-Pedersen C, Hassager C, Køber L. Heart failure etiology impacts survival of patients with heart failure. Int J Cardiol 2011;149:211-5.
Zeitler EP, Eapen ZJ. Anticoagulation in heart failure: A review. J Atr Fibrillation 2015;8:1250.
Rathod SD, Luitel NP, Jordans MJ. Prevalence and correlates of alcohol use in a central Nepal district: Secondary analysis of a population-based cross-sectional study. Glob Ment Health (Camb) 2018;5:e37.
Luitel NP, Baron EC, Kohrt BA, Komproe IH, Jordans MJ. Prevalence and correlates of depression and alcohol use disorder among adults attending primary health care services in Nepal: A cross sectional study. BMC Health Serv Res 2018;18:215.
Maisch B. Alcoholic cardiomyopathy: The result of dosage and individual predisposition. Herz 2016;41:484-93.
Lip GY, Heinzel FR, Gaita F, Juanatey JR, Le Heuzey JY, Potpara T, et al
. European Heart Rhythm Association/Heart Failure Association joint consensus document on arrhythmias in heart failure, endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Eur J Heart Fail 2015;17:848-74.
Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN, Department of Veterans Affairs Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. QRS duration and mortality in patients with congestive heart failure. Am Heart J 2002;143:1085-91.
Iyngkaran P, Liew D, Neil C, Driscoll A, Marwick TH, Hare DL. Moving from heart failure guidelines to clinical practice: Gaps contributing to readmissions in patients with multiple comorbidities and older age. Clin Med Insights Cardiol 2018;12:1179546818809358.
Guha S, Harikrishnan S, Ray S, Sethi R, Ramakrishnan S, Banerjee S, et al
. CSI position statement on management of heart failure in India. Indian Heart J 2018;70 Suppl 1:S1-72.
Nissenson AR, Goodnough LT, Dubois RW. Anemia: Not just an innocent bystander? Arch Intern Med 2003;163:1400-4.
Metra M, Cotter G, Gheorghiade M, Dei Cas L, Voors AA. The role of the kidney in heart failure. Eur Heart J 2012;33:2135-42.
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr., Drazner MH, et al
. 2013 ACCF/AHA guideline for the management of heart failure: Executive summary: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:1495-539.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]